Date post: | 21-Dec-2015 |
Category: |
Documents |
View: | 225 times |
Download: | 1 times |
Cancer Gene Therapy
…Using Tumor Suppressor Genes.
Overview
Gene Therapy p53 Using Gene Therapy to Treat Lung Cancer Problems
Gene Therapy
Vectors In Vivo vs. Ex Vivo Which cells are the target cells
What is Gene Therapy?
Gene therapy is a technique for introducing the genetic material of a gene in a patient that lacks that gene because of a mutation.
Vectors
The way you insert the “normal” gene in the patient’s cell is by vectors.
The most common vectors that are used in gene therapy are virus vectors
Why Viruses?
Viruses through the time of evolution have evolved to infect the cells with great specificity
Viruses tend to be very efficient at transfecting their own DNA into the host cell genome.
This allows them to produce new viral particles at the period of synthesis of the cell
Types Of Viruses…
Retrovirus Adinovirus Lentiviruses Poxviruses and Herpes Viruses
Adenovirus
36 kb Double Stranded DNA Genome
Entry through CAR receptor and integrin co-receptor
E1A E3 E1B
E2A E4E2B
L1 L2 L4L3 L5
Latest Generation Adenoviral Vector
“Gutless”; Helper-dependent; Minimal Ad
Therapeutic Transgene
Stuffer DNAStuffer DNA ITRITR
Which Virus to Use?
Depends how well they transfer the genes to cells which cells they can recognize and infect and whether they alter the cell’s DNA permanently
or temporarily
Cells removed from body
Transgene deliveredCells cultured
Cells returned to the body
Ex Vivo In Vivo
Transgene delivereddirectly into host
Strategies for Transgene Delivery
Which cells are the target cells
Both Healthy and Cancerous cells can be
a target Ex of targeting Healthy cells
One way is by replacing a missing or altered gene with a “normal” one
Cont: Which cells are the target cells Ex of targeting Cancer Cells
Scientists can target cancer cells with genes that can be used to destroy the cells. In this technique, cancer cells are introduced to what is called “suicide genes”
Naked DNANaked DNATarget Target
CellCell
Therapeutic Therapeutic ProteinProtein
AAVAAV
Retrovirus/LentivirusRetrovirus/Lentivirus
AdenovirusAdenovirus
NucleusNucleus
Gene Therapy Principles
Adenovirus Cell Entry
p53 Pathway
Using Gene Therapy to Treat Lung Cancer In this clinical trial the scientist used gene
therapy in combination with radiation therapy so they can treat lung cancer in 19 different patients
Treatment: Gene therapy and Radiation. Intratumoral needle injections of Ad-p53
on days 1, 18 and 32 of the treatment. tumors ≥ 4 cm where injected with 10 ml tumors ‹ 4 cm were injected with 3 ml
Radiation therapy
Results
17/19 patients made it through the entire therapy
complete response in 2 patients (11%) partial response in 4 patients (21%) stable disease in 1 patient (5%) progressive disease in 11 patients (57%)
Results Not That Good
57% of the patients showed that the cancer progressed to worse stages
Why?
Major Problems that Scientists Must Overcome Identify more efficient ways to deliver the
genes to the patients’ genetic material Develop vectors that can specifically focus
on the targeted cells Ensure that vectors will successfully insert
the desired genes into each of these target cells
Cont: Major Problems that Scientists Must Overcome Deliver genes to a precise location in the
patient’s DNA Ensure that transplanted genes are
precisely controlled by the body’s normal physiologic signals